Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS.

Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 µg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin.

Comparison of Doppler ultrasonography and high-definition oscillometry for blood pressure measurements in healthy awake dogs.

OBJECTIVE: To determine the intra- and interobserver variability of systolic arterial pressure (SAP) and diastolic arterial pressure (DAP) measurements obtained with 2 indirect methods in awake dogs and percentage of successful measurements. ANIMALS: 6 healthy conscious adult dogs. PROCEDURES: 4 observers with different levels of training measured SAP and DAP on 4 days by use of Doppler ultrasonography (DU) and high-definition oscillometry (HDO). The examinations were randomized. Measurements for each technique were recorded 5 consecutive times, and mean values (total, 720 measurements) were used for statistical analysis. RESULTS: All within- and between-day coefficients of variation (CVs) for SAP were < 15% irrespective of the observer or method (HDO, 3.6% to 14.1%; DU, 4.1% to 12.4%). Conversely, half the CVs for DAP were > 15% with the highest within- and between-day CVs obtained by the least experienced observer by use of DU (19.5% and 25.9%, respectively). All attempts with HDO were successful, whereas DAP could not be measured by use of DU by the least experienced observer in 17% of attempts. CONCLUSIONS AND CLINICAL RELEVANCE: SAP may be assessed in healthy dogs by use of DU and HDO with good repeatability and reproducibility after a short period of training. Conversely, the variability of DAP is higher and longer training is required to assess DAP via DU than via HDO.

Chordae tendineae rupture in dogs with degenerative mitral valve disease: prevalence, survival, and prognostic factors (114 cases, 2001-2006).

BACKGROUND: Degenerative mitral valve disease (MVD) is the most common heart disease in small breed dogs, and chordae tendineae rupture (CTR) is a potential complication of this disease. The survival time and prognostic factors predictive of survival in dogs with CTR remain unknown. HYPOTHESIS: The prevalence and prognosis of CTR in dogs with MVD increases and decreases, respectively, with heart failure class. ANIMALS: This study used 706 dogs with MVD. METHODS: The diagnosis of CTR was based on a flail mitral leaflet with the tip pointing into the left atrium during systole, which was confirmed in several 2-dimension imaging planes using the left and right parasternal 4-chamber views. RESULTS: CTR was diagnosed in 114 of the 706 dogs with MVD (16.1%) and most of these (106/114, 93%) had severe mitral valve regurgitation as assessed by color Doppler mode. CTR prevalence increased with International Small Animal Cardiac Health Council (ISACHC) clinical class (i.e., 1.9, 20.8, 35.5, and 69.6% for ISACHC classes Ia, Ib, II, and III, respectively [P < .05]). Long-term follow-up was available for 57 treated dogs (angiotensin-converting enzyme inhibitors and diuretics) and 58% of these (33/57) survived > 1 year after initial CTR diagnosis (median survival time, 425 days). Clinical class, the presence of ascites or acute dyspnea at the time of diagnosis, heart rate, plasma urea concentration, and left atrial size were predictors of survival. CONCLUSIONS AND CLINICAL RELEVANCE: CTR is associated with a higher overall survival time than previously supposed. Its prognosis mostly depends on a combination of clinical and biochemical factors.

Assessment of regional systolic and diastolic myocardial function using tissue Doppler and strain imaging in dogs with dilated cardiomyopathy.

BACKGROUND: Tissue Doppler Imaging (TDI) or strain (St) imaging could provide sensitive indices for early detection and treatment follow-up of canine dilated cardiomyopathy (DCM). Analysis of TDI and St features in dogs with overt DCM is a prerequisite before using these new criteria in prospective screenings of predisposed families or in clinical trials. HYPOTHESIS: Radial and longitudinal right and left myocardial motion, assessed by TDI and St variables, is altered in dogs with DCM. ANIMALS: Case records for 26 dogs; 14 with DCM and 12 healthy controls of comparable age and weight were reviewed. METHODS: A retrospective analysis was conducted of conventional echocardiography, 2-dimensional color TDI, and St imaging data. RESULTS: The DCM group was characterized by decreases in radial and longitudinal systolic velocity gradients of the left ventricular free wall (LVFW), radial and longitudinal absolute values of peak systolic St of the LVFW, and longitudinal systolic right ventricular (RV) velocities (all P < .001 versus control) associated with longitudinal postsystolic contraction waves in 7/14 dogs. Early diastolic LVFW velocities also were decreased for longitudinal (P < .01) and radial (P < .05) motions. All radial LVFW, longitudinal basal LVFW, and RV systolic velocities were negatively correlated with heart rate (P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: LV contractility along both the short and long axes is impaired in dogs with spontaneous DCM, as is systolic RV and diastolic LVFW function. These myocardial alterations are associated with an inverse force-frequency relationship. Studies now are needed to determine the comparative sensitivity of TDI and St variables for the early detection of canine DCM.

Diagnostic value of echo-Doppler and tissue Doppler imaging in dogs with pulmonary arterial hypertension.

BACKGROUND: Diagnosis of pulmonary arterial hypertension (PAH) relies on Doppler measurement of pulmonic and tricuspid regurgitation (TR). However, these are not always detectable. HYPOTHESIS: Tissue Doppler imaging (TDI), a novel noninvasive ultrasound technique, provides indirect but sensitive and specific assessment of elevated systolic pulmonary artery pressure (SPAP) in dogs. ANIMALS: One hundred and five dogs with TR. METHODS: Prospective observational study. Dogs were categorized as presenting normal (group 1, n = 45), mildly increased (group 2, n = 19), or moderately to severely increased (group 3, n = 41) SPAP, based on TR peak velocities (< 2.5, 2.5-3.0, and > 3.0 m/s, respectively). Ten quantitative echo-Doppler- and TDI-derived variables were assessed, including the main pulmonary arterial diameter to aortic diameter ratio, pulmonary flow acceleration time, and acceleration-to-ejection time ratio, the Tei index of right ventricular function, and 6 longitudinal basal right ventricular TDI variables. RESULTS: A significant correlation was observed between SPAP and each of the 10 tested variables (P < .05). Conventional echo-Doppler variables were less discriminating than the TDI for predicting increased SPAP. The combined systolic and diastolic right TDI index had the highest sensitivity and specificity (89% and 93% respectively, for a cutoff of 11.8 cm/s) and could discriminate between dogs in group 1 from dogs in group 2. CONCLUSIONS AND CLINICAL IMPORTANCE: TDI provided effective predictors of systolic PAH and demonstrated that both alterations in right-sided systolic and diastolic myocardial function can occur with mild increases in SPAP.

Comparative adverse cardiac effects of pimobendan and benazepril monotherapy in dogs with mild degenerative mitral valve disease: a prospective, controlled, blinded, and randomized study.

BACKGROUND: Pimobendan (PIMO) is an inodilator that may have some beneficial effects in canine degenerative mitral valve disease (MVD). However, little information is available about its cardiac effects in dogs without systolic myocardial dysfunction. HYPOTHESIS: Compared to benazepril (BNZ), an angiotensin-converting enzyme inhibitor, PIMO may worsen valve regurgitation in early canine MVD. ANIMALS: Twelve Beagles with asymptomatic MVD were randomized into 2 groups (n = 6) receiving BNZ or PIMO at dosages of 0.25 mg/kg PO q24h and q12h respectively, for 512 days. METHODS: The study followed a blinded, randomized, prospective, and parallel group design. After day 512, the dogs were necropsied, and cardiac histopathology was performed in a blinded manner. RESULTS: A significant treatment effect was observed as soon as day 15 with increased systolic function in the PIMO group by comparison to baseline value as assessed by fractional shortening (P < .0001) and tissue Doppler variables (P = .001). Concurrently, the maximum area and peak velocity of the regurgitant jet signal increased (P < .001), whereas these variables remained stable in the BNZ group. Histologic grades of mitral valve lesions were more severe in the PIMO group than in the BNZ group. Moreover, acute focal hemorrhages, endothelial papillary hyperplasia, and infiltration of chordae tendinae with glycosaminoglycans were observed in the mitral valves of dogs from the PIMO group but not in those of the BNZ group. CONCLUSIONS AND CLINICAL IMPORTANCE: PIMO has adverse cardiac functional and morphologic effects in dogs with asymptomatic MVD. Additional investigation in dogs with symptomatic MVD is now warranted.

Azotemia and glomerular filtration rate in dogs with chronic valvular disease.

BACKGROUND: Little information is available about the prevalence of renal dysfunction in dogs with chronic valvular heart disease (CVD). HYPOTHESIS: Azotemia and a decrease in glomerular filtration rate (GFR) are more severe with increased severity of CVD. ANIMALS: 124 (study No. 1) and 24 (study No. 2) client-owned dogs with CVD. METHODS: A retrospective study (study No. 1) was performed to assess the prevalence of azotemia in the New York Heart Association (NYHA) classes of heart failure in dogs with CVD. A prospective study (study No. 2) was then designed to determine GFR in dogs with different degrees of CVD severity. Complete physical examination, electrocardiography, blood pressure measurement, thoracic radiographs, echocardiography, and plasma and urine analyses were also performed. RESULTS: In study No. 1, 50% of the dogs were azotemic and the percentage of azotemic dogs increased with functional class (up to 70% in NYHA class IV patients). In study No. 2, 8/24 dogs were azotemic. Plasma urea and creatinine were higher in NYHA class III-IV dogs compared with class I-II dogs. The GFR was lower (P < .001) in NYHA class III-IV dogs (1.7 +/- 0.7 mL/min/kg) than in class I to II dogs (3.1 +/- 0.8 mL/min/kg). Only 1 dog in class I-II had a GFR below 2 mL/min/kg and only 2/9 class III-IV dogs had a GFR above 2 mL/min/kg. CONCLUSION AND CLINICAL RELEVANCE: Azotemia and renal impairment increase with the severity of congestive heart failure and are frequent findings in dogs with CVD. It remains to be shown if deterioration of renal function is a direct result of progression of the heart disease.

Quantification of mitral valve regurgitation in dogs with degenerative mitral valve disease by use of the proximal isovelocity surface area method.

OBJECTIVE: To determine the within-day and between-day variability of regurgitant fraction (RF) assessed by use of the proximal isovelocity surface area (PISA) method in awake dogs with degenerative mitral valve disease (MVD), measure RF in dogs with MVD, and assess the correlation between RF and several clinical and Doppler echocardiographic variables. DESIGN: Prospective study. ANIMALS: 6 MVD-affected dogs with no clinical signs and 67 dogs with MVD of differing severity (International Small Animal Cardiac Health Council [ISACHC] classification). PROCEDURES: The 6 dogs were used to determine the repeatability and reproducibility of the PISA method, and RF was then assessed in 67 dogs of various ISACHC classes. Mitral valve regurgitation was also assessed from the maximum area of regurgitant jet signal-to-left atrium area (ARJ/LAA) ratio determined via color Doppler echocardiographic mapping. RESULTS: Within- and between-day coefficients of variation of RF were 8% and 11%, respectively. Regurgitation fraction was significantly correlated with ISACHC classification and heart murmur grade and was higher in ISACHC class III dogs (mean +/- SD, 72.8 +/- 9.5%) than class II (57.9 +/- 20.1%) or I (40.7 +/- 19.2%) dogs. Regurgitation fraction and left atriumto-aorta ratio, fractional shortening, systolic pulmonary arterial pressure, and ARJ/LAA ratio were significantly correlated. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that RF is a repeatable and reproducible variable for noninvasive quantitative evaluation of mitral valve regurgitation in awake dogs. Regurgitation fraction also correlated well with disease severity. It appears that this Doppler echocardiographic index may be useful in longitudinal studies of MVD in dogs.

Ultrasonographic assessment of regional radial and longitudinal systolic function in healthy awake dogs.

BACKGROUND: Strain (St) and strain rate (SR) imaging are new ultrasound modalities based on tissue Doppler imaging (TDI) that allow quantitative assessment of segmental myocardial contraction or stretching and rate of deformation, respectively. HYPOTHESIS: Regional peak systolic St and SR could allow repeatable and reproducible assessment of systolic function of the right (RVW) and left (LVFW) myocardial walls in dogs. ANIMALS: Six healthy Beagle dogs were used to determine the repeatability and reproducibility of regional peak systolic St and SR in the RVW and LVFW (Study 1). These variables were also assessed in 30 healthy dogs of several breeds (Study 2). METHODS: Longitudinal peak systolic St and SR were recorded in 2 segments (basal and apical) of the RVW and LVFW. Radial peak systolic St and SR of the LVFW were also assessed. RESULTS: All within- and most (7/10) between-day coefficients of variation were <15%. Absolute values of the longitudinal deformation indices were significantly higher (P < .001) in the RVW (St = -39.5 +/- 5.5% and SR = -5.2 +/- 0.8 s(-1) at the base; St = -36.3 +/- 4.3% and SR = -4.7 +/- 1.1 s(-1) at the apex) than in the LVFW. Absolute values were also higher for the radial (St = 62.9 +/- 10.4% and SR = 5.8 +/- 1.1 s(-1), P < .001) than for the longitudinal LFVW motions. CONCLUSIONS AND CLINICAL IMPORTANCE: St and SR imaging is a repeatable and reproducible method for assessing systolic myocardial function. The combination of these indices with conventional echocardiographic variables may be useful for screening canine myocardial diseases.

Tissue Doppler imaging for detection of radial and longitudinal myocardial dysfunction in a family of cats affected by dystrophin-deficient hypertrophic muscular dystrophy.

Diagnosis of feline hypertrophic cardiomyopathy currently is based on the presence of myocardial hypertrophy detected using conventional echocardiography. The accuracy of tissue Doppler imaging (TDI) for earlier detection of the disease has never been described. The objective of this sudy was to quantify left ventricular free wall (LVFW) velocities in cats with hypertrophic muscular dystrophy (HFMD) during preclinical cardiomyopathy using TDI. The study animals included 22 healthy controls and 7 cats belonging to a family of cats with HFMD (2 affected adult males, 2 heterozygous adult females, one 2.5-month-old affected male kitten, and 2 phenotypically normal female kittens from the same litter). All cats were examined via conventional echocardiography and 2-dimensional color TDI. No LVFW hypertrophy was detected in the 2 carriers or in the affected kitten when using conventional echocardiography and histologic examination, respectively. The LVFW also was normal for 1 affected male and at the upper limit of normal for the 2nd male. Conversely, LVFW dysfunction was detected in all affected and carrier cats with HFMD when using TDI. TDI consistently detects LVFW dysfunction in cats with HFMD despite the absence of myocardial hypertrophy. Therefore, TDI appears more sensitive than conventional echocardiography in detecting regional myocardial abnormalities.

Quantitative assessment of velocities of the annulus of the left atrioventricular valve and left ventricular free wall in healthy cats by use of two-dimensional color tissue Doppler imaging.

OBJECTIVE: To analyze velocities of the annulus of the left atrioventricular valve and left ventricular free wall (LVFW) in a large population of healthy cats by use of 2-dimensional color tissue Doppler imaging (TDI). ANIMALS: 100 healthy cats (0.3 to 12.0 years old; weighing 1.0 to 8.0 kg) of 6 breeds. PROCEDURE: Radial myocardial velocities were recorded in an endocardial and epicardial segment, and longitudinal velocities were recorded in 2 LVFW segments (basal and apical) and in the annulus of the left atrioventricular valve. RESULTS: LVFW velocities were significantly higher in the endocardial than epicardial layers and significantly higher in the basal than apical segments. For systole, early diastole, and late diastole, mean +/- SD radial myocardial velocity gradient (MVG), which was defined as the difference between endocardial and epicardial velocities, was 2.2 +/- 0.7, 3.3 +/- 1.3, and 1.8 +/- 0.7 cm/s, respectively, and longitudinal MVG, which was defined as the difference between basal and apical velocities, was 2.7 +/- 0.8, 3.1 +/- 1.4, and 2.1 +/- 0.9 cm/s, respectively. A breed effect was documented for several TDI variables; therefore, reference intervals for the TDI variables were determined for the 2 predominant breeds represented (Maine Coon and domestic shorthair cats). CONCLUSIONS AND CLINICAL RELEVANCE: LVFW velocities in healthy cats decrease from the endocardium to the epicardium and from the base to apex, thus defining radial and longitudinal MVG. These indices could complement conventional analysis of left ventricular function and contribute to the early accurate detection of cardiomyopathy in cats.

Quantitative assessment of regional right ventricular myocardial velocities in awake dogs by Doppler tissue imaging: repeatability, reproducibility, effect of body weight and breed, and comparison with left ventricular myocardial velocities.

Right ventricular myocardial (RVM) motion is poorly documented. The objective of this study was to determine the variability of RVM velocities by tissue Doppler imaging (TDI) in healthy dogs (study 1), to analyze RVM motion in a large healthy canine population (study 2), and to compare the results with those obtained for the left ventricular free wall. Six healthy Beagle Dogs were monitored in study 1, and 64 healthy dogs of 14 different breeds were monitored in study 2. Velocities were recorded in 2 segments (basal and apical) of the right and left myocardial walls. In study 1, 36 TDI examinations were performed for 4 days, whereas a single TDI examination was performed on each dog in study 2. All velocity profiles included 1 positive systolic wave and 2 negative diastolic waves. The lowest intraday and interday coefficient of variation values of the right TDI variables were observed at the base (3.5-16.1%). The variability of the right apical velocities was much higher, with most coefficient of variation values > 15%. RVM velocities were higher in the basal than in the apical segments (P < .001) and were higher than the left velocities of the corresponding segment (P < .01). Body weight and breed had an effect on only a few right and left TDI variables. TDI provides a repeatable and reproducible method for evaluating basal RV function in the dog. These data also demonstrate the heterogeneity of the myocardial velocities between the left and the right ventricles and between the base and the apex.

Reference range values of regional left ventricular myocardial velocities and time intervals assessed by tissue Doppler imaging in young nonsedated Maine Coon cats.

OBJECTIVE: To describe and analyze the left ventricular free wall (LVFW) radial and longitudinal motions in a population of healthy Maine Coon cats by use of quantitative 2-dimensional color tissue Doppler imaging (TDI). ANIMALS: 23 healthy young Maine Coon cats (mean +/- SD: age, 2.1 +/- 0.9 years; weight, 5.0 +/- 1.0 kg). PROCEDURE: TDI was performed by the same trained observer (VC) on all cats. Radial LVFW velocities were recorded in endocardial and epicardial LVFW segments, and longitudinal velocities were recorded in the mitral annulus and in basal and apical LVFW segments. Isovolumic contraction and relaxation times were calculated in each myocardial segment, and the coefficients of variation (CVs; %) were determined for each TDI parameter. RESULTS: LVFW velocities were significantly higher in the endocardial layers than in the epicardial layers and also significantly higher in the basal than in the apical segments. Annular velocities were significantly higher than basal myocardial velocities in systole and early diastole. Coefficient of variation values were lower for radial velocities, particularly in systole, and were also lower for time intervals (16% to 22%) than for myocardial velocities (19% to 62%). CONCLUSIONS AND CLINICAL RELEVANCE: Because Maine Coon cats are predisposed to an inherited hypertrophic cardiomyopathy, which is a common cause of death in this breed, TDI could provide a useful tool for early detection of the disease. Tissue Doppler imaging indices may complete the conventional analysis of the left ventricular function in Maine Coon cats. However, the usefulness of TDI indices in the early detection of myocardial dysfunction needs to be clarified.

Use of quantitative two-dimensional color tissue Doppler imaging for assessment of left ventricular radial and longitudinal myocardial velocities in dogs.

OBJECTIVE: To determine left ventricular free wall (LVFW) radial and longitudinal myocardial contraction velocities in healthy dogs via quantitative 2-dimensional color tissue Doppler imaging (TDI). ANIMALS: 100 dogs. PROCEDURE: TDI was used by a single trained observer to measure radial and longitudinal myocardial movement in the LVFW. Radial myocardial velocities were recorded in segments in the endocardial and epicardial layers of the LVFW, and longitudinal velocities were recorded in segments at 3 levels (basal, middle, apical) of the LVFW. RESULTS: LVFW velocities were higher in the endocardial layers than in the epicardial layers. Left ventricular free wall velocities were higher in the basal segments than in the middle and apical segments. Radial myocardial velocity gradients, defined as the difference between endocardial and epicardial velocities, were (mean +/- SD) 2.5 +/- 0.8 cm/s, 3.8 +/- 1.5 cm/s, and 2.3 +/- 0.9 cm/s in systole, early diastole, and late diastole, respectively. Longitudinal myocardial velocity gradients, defined as the difference between basal and apical velocities, were 5.9 +/- 2.2 cm/s, 6.9 +/- 2.5 cm/s, and 4.9 +/- 1.7 cm/s in systole, early diastole, and late diastole, respectively. A breed effect was detected for several systolic and diastolic TDI variables. In all segments, systolic velocities were independent of fractional shortening. CONCLUSIONS AND CLINICAL RELEVANCE: LVFW myocardial velocities decreased from the endocardium to the epicardium and from base to apex, thus revealing intramyocardial radial and longitudinal velocity gradients. These indices could enhance conventional echocardiographic analysis of left ventricular function in dogs. Breed-specific reference intervals should be defined.

Effects of animal position and number of repeated measurements on selected two-dimensional and M-mode echocardiographic variables in healthy dogs.

OBJECTIVE: To evaluate the effects of positioning and number of repeated measurements on intra- and interobserver variability of echocardiographic measurements in dogs. DESIGN: Prospective study. ANIMALS: 4 healthy dogs. PROCEDURE: Each observer performed 24 examinations, separately assessing each dog 6 nonconsecutive times (3 times with the dog in lateral recumbency and 3 with the dog in a standing position). Variables evaluated included M-mode measurements of left ventricular end-diastolic and left ventricular end-systolic diameters, left ventricular free-wall thickness in diastole and systole, interventricular septal thickness in diastole and systole, left ventricular shortening fraction, and 2-dimensional measurements of the left atrial diameter-to-aortic diameter ratio. RESULTS: All coefficients of variation (range, 3.4% to 26.6%) were similar between operators and positions and were < 15% for 27 of 32 values. For both operators, repeatability of the measurements was better for left ventricular end-systolic diameter, left ventricular free-wall thickness in diastole, left ventricular free-wall thickness in systole, and the left atrial diameter-to-aortic diameter in the standing position, and similar for both positions for shortening fraction and left ventricular end-diastolic diameter. No effect of cardiac cycle was observed. CONCLUSIONS AND CLINICAL RELEVANCE: Within-day variability of conventional echocardiography performed with the dog in the standing position was at least as good as that obtained with the dog in lateral recumbency for most measured variables. Single measurements of each variable may be sufficient for trained observers examining dogs that do not have an arrhythmia. The standing position should be used, particularly for stressed or dyspneic dogs.

Use of tissue Doppler imaging to confirm the diagnosis of dilated cardiomyopathy in a dog with equivocal echocardiographic findings.

A 1-year-old healthy female Great Dane was referred for an echocardiographic examination prior to anesthesia and surgical correction of prolapse of the right third eyelid gland. Findings of a physical examination were normal. Conventional 2-dimensional and M-mode echocardiography revealed equivocal findings of dilated cardiomyopathy (DCM). Conversely, tissue Doppler imaging revealed a dramatic decrease in systolic and early diastolic radial myocardial velocity gradients, which were related to a decrease in endocardial velocities. Four months later, the diagnosis of DCM was confirmed via conventional echocardiography. In dogs with equivocal conventional echocardiographic findings of DCM, severe myocardial alterations may be detected via tissue Doppler imaging and this technique may enable early diagnosis of radial myocardial dysfunction.

Cardiovascular effects of dietary salt intake in aged healthy cats: a 2-year prospective randomized, blinded, and controlled study.

High salt dry expanded diets are commercially available for cats to increase water intake and urine volume, as part of the prevention or treatment of naturally occurring urinary stone formation (calcium oxalates and struvites). However, chronic high salt intake may have potential cardiovascular adverse effects in both humans, especially in aging individuals, and several animal models. The objective of this prospective, randomized, blinded, and controlled study was to assess the long-term cardiovascular effects of high salt intake in healthy aged cats. Twenty healthy neutered cats (10.1 ± 2.4 years) were randomly allocated into 2 matched groups. One group was fed a high salt diet (3.1 g/Mcal sodium, 5.5 g/Mcal chloride) and the other group a control diet of same composition except for salt content (1.0 g/Mcal sodium, 2.2 g/Mcal chloride). Clinical examination, systolic and diastolic arterial blood pressure measurements, standard transthoracic echocardiography and conventional Doppler examinations were repeatedly performed on non-sedated cats by trained observers before and over 24 months after diet implementation. Radial and longitudinal velocities of the left ventricular free wall and the interventricular septum were also assessed in systole and diastole using 2-dimensional color tissue Doppler imaging. Statistics were performed using a general linear model. No significant effect of dietary salt intake was observed on systolic and diastolic arterial blood pressure values. Out of the 33 tested imaging variables, the only one affected by dietary salt intake was the radial early on late diastolic velocity ratio assessed in the endocardium of the left ventricular free wall, statistically lower in the high salt diet group at 12 months only (P = 0.044). In conclusion, in this study involving healthy aged cats, chronic high dietary salt intake was not associated with an increased risk of systemic arterial hypertension and myocardial dysfunction, as observed in some elderly people, salt-sensitive patients and animal models.

Bradykinin restores left ventricular function, sarcomeric protein phosphorylation, and e/nNOS levels in dogs with Duchenne muscular dystrophy cardiomyopathy.

AIMS: Cardiomyopathy is a lethal result of Duchenne muscular dystrophy (DMD), but its characteristics remain elusive. The golden retriever muscular dystrophy (GRMD) dogs produce DMD pathology and mirror DMD patient's symptoms, including cardiomyopathy. We previously showed that bradykinin slows the development of pacing-induced heart failure. Therefore, the goals of this research were to characterize dystrophin-deficiency cardiomyopathy and to examine cardiac effects of bradykinin in GRMD dogs. METHODS AND RESULTS: At baseline, adult GRMD dogs had reduced fractional shortening (28 ± 2 vs. 38 ± 2% in control dogs, P < 0.001) and left ventricular (LV) subendocardial dysfunction leading to impaired endo-epicardial gradient of radial systolic velocity (1.3 ± 0.1 vs. 3.8 ± 0.2 cm/s in control dogs, P < 0.001) measured by echocardiography. These changes were normalized by bradykinin infusion (1 µg/min, 4 weeks). In isolated permeabilized LV subendocardial cells of GRMD dogs, tension-calcium relationships were shifted downward and force-generating capacity and transmural gradient of myofilament length-dependent activation were impaired compared with control dogs. Concomitantly, phosphorylation of sarcomeric regulatory proteins and levels of endothelial and neuronal nitric oxide synthase (e/nNOS) in LV myocardium were significantly altered in GRMD dogs. All these abnormalities were normalized in bradykinin-treated GRMD dogs. CONCLUSIONS: Cardiomyopathy in GRMD dogs is characterized by profound LV subendocardial dysfunction, abnormal sarcomeric protein phosphorylation, and impaired e/nNOS, which can be normalized by bradykinin treatment. These data provide new insights into the pathophysiological mechanisms accounting for DMD cardiomyopathy and open new therapeutic perspectives.

Prevalence of the MYBPC3-A31P mutation in a large European feline population and association with hypertrophic cardiomyopathy in the Maine Coon breed.

OBJECTIVES: The MYBPC3-A31P mutation has been identified in the USA in a colony of Maine Coon cats with an autosomal dominant hypertrophic cardiomyopathy (HCM). The objectives of this prospective study were: 1) to evaluate the prevalence of this mutation in a large feline population from Europe; 2) to compare these data with the prevalence of HCM in the Maine Coon breed. ANIMALS AND METHODS: 1) 3757 cats from different breeds including 2744 Maine Coon cats were screened for the mutation. 2) 164/2744 Maine Coon cats were subjected to echocardiography (Echo-Group, mean age = 2.6 years [0.3-11.5]). RESULTS: 1) In the whole study population, the mutation was only found in Maine Coon cats (prevalence = 41.5%), except for one British Longhair cat. 2) 55/164 (34%) cats from the Echo-Group carried the mutation while only 12/164 (7%; 5/48 heterozygous, 5/7 homozygous mutated, 2/109 homozygous wild-type cats) showed HCM. MYBPC3-A31P was associated with a significant increased risk of HCM (relative risk = 9.91). CONCLUSION: The MYBPC3-A31P mutation is highly prevalent in Maine Coon cats in Europe and appears to be breed specific with potential marginal events. Young unaffected mutated cats and affected homozygous wild-type cats illustrate the phenotypic and etiological heterogeneity of feline HCM, as demonstrated in humans.

Ante-mortem diagnosis of persistent truncus arteriosus in an 8-year-old asymptomatic dog.

Persistent truncus arteriosus (PTA) was diagnosed in an 8-year-old neutered male Poodle referred for echocardiographic examination prior to anesthesia for surgical correction of bilateral cataract. A single large artery limited by a bicuspid valve and overriding both ventricles was observed with 2 distinct pulmonary arteries arising from the common arterial trunk. A large size interventricular septal defect was associated with a low velocity bidirectional shunt. The lesion was identified as a Type 3 PTA according to Collett and Edwards' classification. Although no clinical signs were reported, the dog presented polycythemia (packed cell volume=68%) at the time of diagnosis. To our knowledge, this is the first report of an echocardiographic diagnosis of PTA in the dog. Until now, the ante-mortem diagnosis of this congenital heart disease has only been described in the cat. This case is also of interest because of the age of the animal and the total absence of cardio-respiratory signs at the time of diagnosis.